The objectives of this proposal are: a) detailed structural and mechanistic understanding of the synthetic organic chemistry of the furocoumarins and their functionally substituted analogs; b) an understanding of the photochemistry of these compounds with nucleic acids which will include a rigorous structure determination of the product of photochemistry, the effects of functional substitution on photoreactivity, and an analysis of the base sequence specificity and helical structure dependence on these reactions; c) the development of chemical reactions capable of cleaving nucleic acid backbones at the positions of psoralen photoaddition, thus providing a mapping method for in vivo intercalation sites in nucleic acid secondary structures; d) the synthesis of effective nucleic acid-nucleic acid photocrosslinking reagents and nucleic acid-protein photocrosslinking reagents as probes to in vivo organelle structure and as chemically specific fixatives.